Background/Purpose
Disease flares are increasingly used as outcomes in axial spondyloarthritis (axSpA) trials or observational studies. The objective of this initiative was to define a cutoff for the ASDAS score that best defines the concept of ‘worsening in axSpA’, to be used in the context of clinical trials and longitudinal observational studies.

Methods
Various steps were followed between 2014 and 2017. after an SLR and a vignette-exercise among ASAS members: a theoretical ‘paper’ patient-vignette. After presentation of the results at the ASAS 2015 meeting it was decided that the proposed cut-off needed to be validated with real-life data. A real-life multicenter international study: data necessary to calculate different outcomes were collected from real patients at 2 consecutive visits (spaced 7 days to 6 months): the external standard was defined as a patient’s report that he/she had worsened and he/she felt there was a need for treatment intensification. Different changes in the outcomes against both external standards for worsening (phy-worsening (vignettes) and pt-worsening) were tested followed by a consensus and voting procedure among ASAS members in January 2017.

Results
(a) There was consensus about worsening being an absolute change between 2 time-points (without defining time between the 2 time-points) and about exploring cutoffs for 3 outcomes: ASDAS-CRP, BASDAI and pain. (b) The literature review had yielded 27 different cutoffs in 38 studies indicating important heterogeneity. (c) The vignette-exercise yielded 12 preliminary definitions for worsening to be tested (as previously reported (ref)). (d) In the prospective study the sensitivity and specificity of each cutoff was tested against pt-worsening and judged by the ASAS-community. (e) No consensus was reached for a BASDAI-based definition due to limited performance of all cut-offs, and it was decided to not define a value for a pain-based definition for worsening. Based on aggregated data (Table), a consensus was reached among the ASAS-members to define worsening as a deterioration in ASDAS of at least 0.9 points. While this cutoff led to only moderate sensitivity when tested against pt-worsening, the overall balance of sensitivity and specificity as well as the overall face validity of this cut-off value for ASDAS was deemed most acceptable.

Table. Sensitivity and specificity of different ASDAS cutoffs to define worsening, against phy-worsening and pt-worsening considered as external standards.

Conclusion
This data-driven ASAS consensus process has allowed to propose an ASDAS-based cutoff value defining worsening in axSpA. As has been observed in other settings, the change defining worsening (at least 0.9) is smaller than the change defining improvement which is 1.2 for ASDAS. This definition should now be applied in trials.

Comment:
Our patients usually tell us whether their disease has improved or worsened since the last consultation. One question raised after the introduction of the Ankylosing Spondylitis Disease Activity Score (ASDAS) refers to the differences in ASDAS that may correspond to a disease flare or improvement. This abstract presents a large ASAS initiative to define these cut-offs and the findings have already been tested in a large group of patients with AS from different countries. The ASDAS change defining worsening is at least 0.9 ASDAS points and the change defining improvement is 1.2 ASDAS points. These definitions will now be applied in clinical trials and observational cohorts. Although these cut-offs are not intended for use in clinical practice, they might help in individual cases to assess response to treatment.